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Immunity. 2017 Aug 15;47(2):374-388.e6. doi: 10.1016/j.immuni.2017.07.018.

A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.

Author information

1
Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: frederis@ansto.gov.au.
2
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, Singapore, Singapore.
3
Systems Immunology, Viral Immunology Systems Program, the Kirby Institute, UNSW, Sydney, NSW, Australia.
4
Antigen Presentation and Immunoregulation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
5
Department of Chemical & Biomolecular Engineering, Materials Characterization and Fabrication Platform, University of Melbourne, Melbourne, VIC, Australia.
6
Centenary Institute and the University of Sydney, Newtown, NSW, Australia.
7
Department of Microbiology and Immunology at Peter Doherty Institute for Infection and Immunity and the ARC Centre of Excellence in Advanced Molecular Imaging at the University of Melbourne, Melbourne, VIC, Australia.
8
Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia.
9
Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia; Immunology Research Centre, St. Vincent's Hospital, Melbourne, VIC, Australia.
10
CERA and ANZAC Research Institute, Concord RG Hospital and University of Sydney, Sydney, NSW, Australia.
11
Centenary Institute and the University of Sydney, Newtown, NSW, Australia; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, Australia.
12
Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: d.bowen@centenary.org.au.
13
Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: p.bertolino@centenary.org.au.

Abstract

The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.

KEYWORDS:

Kupffer cells; Listeria; bacterial infection; dendritic cells; hepatic capsule; liver-resident macrophages; monocytes; neutrophils; niche; peritoneal cavity macrophages

PMID:
28813662
DOI:
10.1016/j.immuni.2017.07.018
[Indexed for MEDLINE]
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